Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stopping fatty change in heart cells

04.06.2009
One molecule is all it takes to set a fatal chain of events in motion that can end up leading to heart failure. Cell biologists at ETH Zurich have discovered why oxygen deficiency causes the myocardial muscle to extract energy from sugar and store fat in the cells.

Heart failure is one of the world's most frequent causes of death - caused by conditions such as diabetes and obesity. With people who are overweight, the heart has to do more work in order to pump the blood through the circulatory system and this causes an increase in blood pressure.

The heart itself becomes enlarged as the myocardial muscle cells increase in mass. To enable the heart to grow there also has to be an increased supply of energy and oxygen. However, the myocardial muscle cells suffer from a lack of oxygen and energy until such time as there are enough blood vessels to support the tissue.

This is the critical moment in which the cells convert their metabolism. A healthy heart burns fat. But the abnormally enlarged heart cells burn sugar in the form of glucose because this form of energy is quickly available. The protein HIF1-alpha is responsible for this conversion to sugar combustion. This has been demonstrated in research work done by Jaya Krishnan from the group of Wilhelm Krek, Professor of Cell Biology at ETH Zurich. His research has just been published in the online journal "Cell Metabolism".

Cells undergo fatty change and die off

However, HIF1-alpha does not merely result in modified metabolism, it also activates other genes. One of the genes regulated by HIF1-alpha is known as PPARgamma. It causes the cardiac cells to produce and store fat. This results in the cells becoming fatty and dying off. Myocardial contraction is disrupted and this can lead to fatal heart failure. With HIF1-alpha, the researchers have identified a protein which has an effect that is not only of significance in connection with heart failure. This protein is in fact the most important catalyst that causes cells to convert glucose into fat.

Healthy heart despite high blood pressure

The researchers working around Krek have discovered an amazing fact - mice lacking the corresponding gene, and by which HIF1-alpha is therefore ineffetive, do not suffer from heart disease. And this does not change even if the mice have high blood pressure. Their hearts also do not enlarge under such conditions of pathologic stress unlike the hearts of normal mice. They burn fat instead of sugar and function like healthy hearts.

At the same time, the research team has been able to provide an explanation for a phenomenon that is especially important to diabetics: some diabetics are given PPARgamma-promoting medicine to help muscles and other organs better respond to insulin. Clinical studies have shown that these patients have a higher risk of dying from heart failure. This research by Krishnan and Krek has shown why these drugs may be risky.

Dream pill in the distant future

In order to combat heart failure, a substance has to be found that binds itself to the protein HIF1-alpha in order to block it. It might be hard to locate a satisfactory antagonist to HIF1-alpha because the protein has no enzymatic docking site. Nevertheless, research is under way to develop a suitable molecule although Professor Wilhelm Krek does not think this will be quickly achieved. He is, however, convinced that with an effective remedy, the burden associated with this disease of civilization can be reduced.

ETH Zurich
Prof. Wilhelm Krek
Institute of Cell Biology
Phone +41 44 633 34 47
wilhelm.krek@cell.biol.ethz.ch

Roman Klingler | idw
Further information:
http://www.ethz.ch

More articles from Life Sciences:

nachricht Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>